Communication among individuals of a species relies on a number of different sensory inputs including chemical, mechanical, auditory, or visual cues (EDWARD O. WILSON, SOCIOBIOLOGY: THE NEW SYNTHESIS (25th anniv ed. 2000)). Chemical signaling is perhaps the most ancient form of interorganismal communication (EDWARD O. WILSON, SOCIOBIOLOGY: THE NEW SYNTHESIS (25th anniv ed. 2000); Wyatt, Nature 457:262-63 (2009)), and analysis of the chemical signals and the behaviors they mediate is of great significance for understanding the ecological and evolutionary dynamics of intra- and inter-specific interactions.
Nematodes are among the most abundant animals in the world, by individual count (SIEVERT LORENZEN: THE PHYLOGENETIC SYSTEMATICS OF FREELIVING NEMATODES (The Ray Society, London, 1994)). They inhabit sulfurous sediment, deep-sea trenches, mammals, insects, plants, arctic ice, and many other habitats, making them one of the most successful groups of animals on earth (Nussbaumer et al., Aquat. Microb. Ecol. 34:239-46 (2004); ISTVÁN ANDRASSY: EVOLUTION AS A BASIS FOR THE SYSTEMATIZATION OF NEMATODES (Budapest, 1976); Tietjen, Deep-Sea Res. 36:1579-94 (1989); Aben-Athar, Rev. Bras. Med. 2:89-94 (1951); Lutz, Weitere Mittheilungen 3: 425-28 (1888); Blaxter, Science 282:2041-46 (1998)). Many nematode behaviors have been studied, such as mate finding in roots, bacteria, sand, agar, and intestines (DONALD L. LEE: THE BIOLOGY OF NEMATODES (CRC Press, London, 2002)). Little is known about nematode pheromone systems. Although there have been many attempts to identify nematode pheromones (DONALD L. LEE: THE BIOLOGY OF NEMATODES (CRC Press, London, 2002)), identification has only been successful in very few species (Jaffe et al., J. Chem. Ecol. 15:2031-43 (1989); Srinivasan et al., Nature 454:1115-18 (2008); Jeong, et al., Nature 433:541-45 (2005); Butcher et al., Nat. Chem. Biol. 7:420-22 (2007); Pungaliya et al., PNAS 19:7708-13 (2009)).
The free-living nematode C. elegans is used extensively as a model system for social behaviors such as foraging, population density sensing, mating, and aggregation (de Bono & Maricq, Annu. Rev. Neurosci. 28:451-501 (2005)). Entomopathogenic nematodes (EPN), such as Heterorhabditis spp. and Steinernema spp. are obligate insect parasites that kill and consume their hosts with the aid of symbiotic bacteria (Kaya & Gaugler, Annu. Rev. Entomol. 38:181-206 (1993)). C. elegans is typically found in decomposing plant material (Barriere & Felix, Curr. Biol. 15:1176-84 (2005)). It completes its life cycle within 3.5 days under standard laboratory conditions. When the conditions are not favorable for normal growth and development, such as high temperature, high density, or low food availability, it forms dauer larvae (alternative 3rd larvae). This specialized life stage, which does not feed and is resistant to stressful conditions (Golden & Riddle, Dev. Biol. 102:368-78 (1984); Golden & Riddle, Science 218:578-80 (1982); Golden & Riddle, PNAS 81:819-23 (1984)), is analogous to infectious juveniles (IJs) of entomopathogenic nematodes and second stage juveniles (J2) of plant parasitic root-knot nematodes (PAUL DE LEY: A QUICK TOUR OF NEMATODE DIVERSITY AND THE BACKBONE OF NEMATODE PHYLOGENY (WormBook, ed. The C. elegans Research Community, 2006)) (Meloidogyne spp) that are equally adapted to survive conditions unfavorable for normal growth and development. Upon depletion of food resources or when overcrowded, IJs of entomopathogenic nematodes and dauer larvae of the free living nematode Caenorhabditis elegans display a dispersal behavior (Golden & Riddle, Dev. Biol. 102:368-78 (1984); Rolston et al., J. Nematol. 38:221-28 (2006); Abebe et al., J. Exp. Biol. 213:3223-29 (2010)).
For C. elegans, entry of early larval stages (L1) into the dauer stage is regulated by a pheromone, called daumone (Jeong et al., Nature 433:541-45 (2005)). Subsequent to the identification of daumone, many related compounds have been found in C. elegans (Butcher et al., Nat. Chem. Biol. 3:420-22 (2007); Butcher et al., PNAS 105:14288-92 (2008); Srinivasan et al., Nature 454:1115-18 (2008); Butcher et al., Org. Lett. 11:3100-03 (2009); Pungaliya et al., PNAS 106:7708-13 (2009); von Reuss et al., J. Am. Chem. Soc. 134(3):1817-24 (2012)). All of these compounds have the unusual dideoxysugar ascarylose and are as a group called ascarosides.
Studies in C. elegans have shown that this family of small-molecule pheromones regulates gender specific attraction, repulsion, aggregation, olfactory plasticity, and entry into dauer (a stress-resistant life stage), collectively demonstrating that ascarosides mediate a wide range of C. elegans behaviors (Srinivasan et al., Nature 454:1115-18 (2008); Macosko et al., Nature 458:1171-75 (2009); Yamada et al., Science 329:1647-50 (2010); Butcher et al., Nat. Chem. Biol. 3:420-22 (2007)). Because ascarosides have not yet been found in any other animal phylum (Bartley et al., J. Nat. Prod. 59(10):921-26 (1996)), ascarosides may comprise a nematode-specific chemical code that may regulate important cues for multiple nematode species. Despite their importance for many aspects of C. elegans biology, however, knowledge of ascaroside structures, biosynthesis, and homeostatis, as well as the extent to which they may be produced and/or affect other nematodes, remained incomplete.
The present invention is directed to overcoming these and other deficiencies in the art.